We have demonstrated that the growth hormone receptor on isolated rate hepatocytes is subject to allosteric regulation. We propose to extend our studies of how peptide hormone binding is regulated by studyin the interactions of insulin and glucagon with isolated liver cells. Hepatocytes will be obtained from normal animals and models in which endogenous hormone levels have been elevated. Cells obtained from normal animals will be subjected to both acute and chronic pulses of hormone. These studies when considered in concert will permit an evaluation of the manner by which receptor site occupancy affects subsequent hormone binding. Studies of a number of biologic endpoints will be directly correlated with the binding studies. This will permit an assessment of whether any particular alteration in cellular response results solely from alterations in the primary cell surface receptor, from a process subsequent to the initial binding interaction or from both of these possibilities. Ultimately, it is hoped that a greater understanding of the relationship between the regulation of cell surface binding of bioregulators and cellular response will permit a more fundamental insight into the basis of cell surface regulation in normal animals and the manner by which this may be altered in metabolically altered animal models.